LDL Oxidation Research Articles

Objectively Measured Vigorous‐Intensity Physical Activity is Related to Endothelial Function in Midlife and Older Men but not in Estrogen‐Deficient Postmenopausal Women

BackgroundAerobic exercise training is consistently associated with enhanced vascular endothelial function via suppression of oxidative stress in midlife/older (ML/O; 50 years) men but not in estrogen‐deficient postmenopausal women (E‐PMW). It is unclear if chronic physical activity (PA) patterns assessed under free‐living conditions, including sedentary behavior and vigorous exercise, are related to endothelial function among ML/O men or E‐PMW. We investigated if objectively measured PA patterns were associated with endothelial function in ML/O adults and the potential mechanisms involved.Methods172 ML/O adults were included for analysis (67 ± 7 years; 85M/87W). Endothelium‐dependent dilation was assessed via brachial artery flow‐mediated dilation (FMDBA), a bioassay of endothelial function. PA was assessed over 3‐7 days via wrist‐worn accelerometers (GENEactiv), which measured sedentary time and light, moderate, and vigorous activity. The relations between endothelial function and PA were examined using simple and stepwise linear regression. Multiple linear regression was used to examine the correlation between endothelial function and PA when controlling for conventional cardiovascular disease risk factors. Plasma oxidized low‐density lipoprotein (OxLDL) concentrations and total antioxidant status were used as markers of oxidative stress and antioxidant defenses, respectively. Interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein concentrations were examined to assess chronic low‐grade inflammation. Mediation analysis was used to determine the potential for changes in oxidative stress, antioxidant defenses, and inflammation as mechanisms mediating the relation between PA and endothelial function.ResultsIn the entire cohort of subjects, FMDBA was negatively associated with sedentary time (R2=0.04; p=0.01), not associated with light PA (R2=0.02; p=0.09), and positively associated with moderate (R2=0.03; p=0.04) and vigorous (R2=0.06; p<0.01) PA. Only sedentary time (R2=0.06; p=0.02) and vigorous PA (R2=0.11; p<0.01) were associated with FMDBA in ML/O men. No PA parameters were associated with FMDBA in E‐PMW (all p>0.05). Stepwise linear regression revealed vigorous PA primarily mediated the effects of PA on FMDBA in ML/O men (R2=0.10; p<0.01). When controlling for age, blood pressure, body mass index, triglycerides, high‐density lipoprotein, low‐density lipoprotein, and fasting glucose, vigorous PA independently predicted FMDBA in ML/O men (R2=0.05; p=0.05) but not in E‐PMW (R2=0.03; p=0.18). Plasma OxLDL concentrations mediated 13.5% of the group effect of vigorous PA on FMDBA (p<0.01); no other plasma markers had a mediating effect (all p>0.05).ConclusionsObjectively measured PA, primarily vigorous PA, is positively associated with endothelial function in ML/O men but not in E‐PMW. This relation is mediated, in part, by oxidative stress. These associations are consistent with findings that aerobic exercise training does not improve endothelial function in E‐PMW. Alternative strategies to improve endothelial function in E‐PMW are needed.

Paraoxonase and vitamin D status in subjects with elevated LDL

Introduction and Aim: Of the various causes for atherosclerosis vitamin D deficiency/insufficiency is well-known. Low levels of vitamin D are linked to alterations in certain markers of cardiovascular disease risk. Paraoxonase (PON-1) protects against CVD by preventing the oxidation of LDL as well as HDL. Reports on the correlation of PON-1 and vitamin-D status are very few. The present study assessed the correlation of PON1 and vitamin-D status in subjects with elevated LDL levels. Materials and Methods: Serum samples of subjects with elevated LDL were assessed for lipid profile, vitamin-D and Paraoxonase. Vitamin D and lipid profile were estimated using COBAS auto-analyzer. Paraoxonase activity was assessed by the spectrophotometric method. 60 subjects with elevated LDL were taken as test and 30 with normal LDL were taken as the control group. Results: Reduction in PON1 activity coupled with low HDL cholesterol and vitamin-D levels was seen in subjects with elevated LDL. Negative correlation of basal PON-1 with LDL was seen in the test group. The control group showed a negative association of Paraoxonase with HDL and a positive association with Vitamin D. Conclusion: Elevated LDL along with vitamin-D deficiency enhances the risk of atherosclerosis. Future interventional studies (dietary supplements and drugs) leading to the enhancement of the PON-1 activity and lower LDL may give more insights on its anti-oxidant role.

Inhibition of LDL Oxidation and Foam Cell Development of Tannin Methanol Extract from Citrus limon and Honey Formulation on Cell lines

Inhibition of LDL Oxidation and Foam Cell Development of Tannin Methanol Extract from Citrus limon and Honey Formulation on Cell lines

Evaluation of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and sLOX-1/oxidized LDL ratio as novel biomarkers of acute coronary syndrome.

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the pathophysiology of atherosclerosis and acute coronary syndromes (ACS). In patients with acute coronary syndrome, circulating soluble LOX-1 (sLOX-1) levels are dramatically elevated. This study aimed to assess sLOX-1 levels in acute coronary syndromes and determine the ratio of sLOX-1 and oxidative LDL in cases of myocardial infarction and unstable angina pectoris and the ROC curve for this ratio sLOX-1. A case-control study was conducted at the department of chemistry and biochemistry, college of medicine, Al- Nahrain University, Baghdad, Iraq, from September 2020 to January 2021. In a total of 90 subjects (30 patients with myocardial infarction within the first six hours of chest pains, 30 patients with unstable angina pectoris, and 30 healthy donors). The ELISA technique measured concentrations of sLOX-1 and oxidized LDL. In addition, Troponin and highly sensitive C reactive protein were measured by the same technique (Fluorescence immune assay), and lipid profile was measured using the Spectrophotometer technique. The median level of sLOX-1 in MI group was 476.17 pg/ml (90.88-675.4 pg/ml) which was significantly higher than that of UA patients (median=289.1 pg/ml [62.74-585.43 pg/ml]) and controls (median=144.52 pg/ml [79.17-283.83 pg/ml]) with highly significant differences and the median sLOX-1/OX-LDL ratio in patients with MI was 64.6 (range 15.17-100.15) which was significantly higher than either patients with UA (median=37.6 [7.06-88.65]) or controls (median=25.29 [12.7-43.04]). There were elevated levels of sLOX-1 in acute coronary syndromes. The sLOX-1/oxidized LDL ratio also strongly indicated the diagnosis and a discriminatory force on the ROC curve for myocardial infarction.

Endothelial-Derived APT1-Mediated Macrophage-Endothelial Cell Interactions Participate in the Development of Atherosclerosis by Regulating the Ras/MAPK Signaling Pathway.

Acyl-protein thioesterase 1 (APT1) can affect H-Ras localization and function by promoting its depalmitoylation. However, relatively little attention has been paid to the effects of APT1 on H-Ras in the cardiovascular system. In this study, we revealed its roles in atherosclerosis development using oxidative low-density lipoprotein (ox-LDL)-induced endothelial dysfunction models and a Western diet-induced ApoE−/− mouse model. The results showed that APT1 expression was up-regulated, while that of miR-138-5p (miR-138) was down-regulated (p < 0.05) in this model. In the meantime, APT1 and H-Ras were translocated from the cytoplasm to the plasma membrane. Bioinformatic analysis and double fluorescence identified miR-138 as the upstream regulator of APT1. APT1 knockdown regulated H-Ras localization and expression, which subsequently affected the MAPK signaling pathway and the expression of its downstream factors. Further research indicated that human umbilical vein endothelial cells (HUVECs)-derived biogenic nanoparticles (BiNPs), hBPs secretion, and RNA expression of hBP-loaded APT1 were increased (p < 0.05) in the ox-LDL induced endothelial dysfunction model. Meanwhile, the HUVECs-derived APT1 could further affect macrophage function through hBP transportation. Altogether, this study demonstrated that the miR-138-APT1 axis may be partially responsible for atherosclerosis development by regulating the H-Ras-MAPK signaling pathway and hBP transportation. The results also shed novel insight on the underlying mechanisms of, and identify potential diagnostic and therapeutic targets for, atherosclerotic cardiovascular diseases in the future.

The beneficial effect of Adansonia digitata products success to modulate lipid profiles and inhibit LDL oxidation in-vitro: An associational study.

There is a growing interest in medicinal plants in recent years due to their many therapeutic benefits and low side effects. Among the medicinal plants is the African Adansonia digitata (baobab) that has edible fruit. In the current study, the effect of A. digitata juice consumption on the lipid profile was investigated. In addition, inhibition of the oxidation of low-density lipoprotein cholesterol (LDL-C) in-vitro by A. digitata essential oil (EO) was also investigated. In this cohort study, a total of 70 subjects of A. digitata users (AD group, 42 male and 28 female) and 70 non A. digitata users (Non-AD group, 44 male and 26 female) were recruited to participate in this study. We evaluated lipid profile, HbA1c, liver/kidney functions, and phytosterol contents in fasting blood samples of all participants. The present findings illustrated significantly lower levels of total cholesterol, triglycerides, and LDL in the AD group compared to Non-AD (p < 0.01). In addition, essential oil of A. digitata inhibited LDL oxidation in-vitro as shown by the significant decreases in the formation of malonaldehyde (MDA), protein carbonyl (PC), and lipid hydroperoxide (LHP) (P<0.05). No significant changes in fasting blood glucose, HbA1c, HDL, kidney function, and liver function enzymes between the two groups were detected (P>0.05). The juice of A. digitata has hypolipidemic and antioxidative effects and might be beneficial for the management of lipid levels in the body.

IDF21-0074 Role of methylglyoxal modified low density lipoprotein in type 2 diabetes mellitus and its role in periodontal disease

Background: Glycation, a physiological and pathological process mainly affects proteins, nucleic acids and lipids. Methylglyoxal (MGO) along with free radicals is known to contribute to the pathogenesis of several diseases, in disorders particularly having enhanced production of acetone and amino-acetone such as diabetes mellitus (DM). The accumulation of MGO induces β-cells dysfunction, insulin resistance as well as impairment of endothelial functions in DM patients. Also, the increased level of MGO intensifies ROS generation and AGEs formation which further accelerates the co-morbidities associated with type 2 diabetes mellitus (T2DM). There is an increased susceptibility and severity of periodontal diseases in case of patients with diabetes and vice-versa. Aim: The likely role of native low density lipoprotein (LDL) and glycated LDL in type 2 diabetes mellitus (T2DM) and periodontitis (PD) as well as in T2DM+PD patients has been evaluated. Method: Sera from T2DM+PD T2DM and PD patients (n=80), were screened for the presence of antibodies against MGO-LDL and native LDL. Besides, the conformational changes in LDL isolated from T2DM+PD, T2DM and PD patients (possibly due to glycoxidaton) were also studied by UV absorption, fluorescence and CD spectroscopy. ThT, Comet assay, SEM and TEM were also done. Cellular toxicity of the isolated LDL from both T2DM+PD, T2DM and PD patients was demonstrated by comet assay. Biochemical parameters like increase in carbonyl content, TBARS, TNF α and IL1β indicate LDL oxidation and increase in pro-inflammatory cytokines. Results: MGO-LDL (in comparison to parallel control) proved to be a potent antigen showing very high binding with T2DM+PD, T2DM and PD sera as observed in direct binding ELISA. The stronger binding of T2DM+PD, T2DM and PD auto-antibodies to MGO-LDL suggests the importance of this modification in the onset and pathogenesis of these diseases. Inhibition ELISA results showed very high percent inhibition of antibodies from T2DM+PD, T2DM and PD patients by MGO-LDL in comparison to native LDL pointing towards the possible role of glycoxidation of LDL in these patients. The modified LDL might have further generated high levels of circulating auto-antibodies in the sera of these patients. Further, to ascertain the specificity of auto-antibodies from T2DM+PD, T2DM and PD patients, competitive inhibition ELISA studies were done on IgG isolated from the sera of these patients. The samples of isolated IgG from T2DM+PD (T2DM+PD-IgG), T2DM (T2DM-IgG) and PD (PD-IgG) showed very strong recognition of MGO-LDL in comparison to the native counterpart. The specificity and affinity of T2DM+PD, T2DM and PD auto-antibodies towards MGO-LDL was further confirmed by gel retardation assay. The gel mobility results confirmed specificity of MGO-LDL towards auto-antibodies from T2DM and PD patients. Furthermore, high recognition of experimentally induced anti-MGO-LDL antibodies by T2DM+PD-LDL, T2DM-LDL and PD-LDL compared to NHS-LDL confirmed that the observed structural damage in T2DM+PD-LDL, T2DM-LDL and PD-LDL is due to glycoxidation. Discussion: The neo-epitopes on LDL created by its exposure to MGO appear to be responsible for induction and elevated levels of these antibodies, and thus MGO-LDL may be considered as potential antigenic candidate for auto-immune response in diabetes and periodontitis patients with a potential for biomarker development.

Role of a Novel Silver Fir (Abies alba) Extract, Abigenol®/AlbiPhenol®, in Modulating Cardiovascular Disorders: Key Factors.

Cardiovascular diseases (CVDs) represent the leading cause of death worldwide, being responsible for about one third of deaths. Among CVDs, coronary artery diseases (CADs) are characterized by vascular endothelium dysfunction due to oxidative and inflammatory damages, the oxidation of circulating low-density lipoproteins (LDL) and high-density lipoproteins (HDL), and the production of ROS in the steatotic liver with the consequent increase of lipids and cholesterol. Together with CADs, heart failure (HF) represents another high-mortality rate CVD. A major risk factor for HF is hypertension that is accompanied by oxidative stress. Phytoextracts, rich in antioxidant and anti-inflammatory compounds, may have therapeutic value as they can interfere with several CVDs risk factors. In this work, a novel silver fir (Abies alba) bark extract, Abigenol®/AlbiPhenol®, was studied. First, Abigenol®/AlbiPhenol® cytotoxicity, bioaccessibility and bioavailability were evaluated by using an in vitro digestion model. Abigenol®/AlbiPhenol® was shown to be non-cytotoxic and showed good bioaccessibility. Then, by using in vitro hepatic, cardiac and vascular models, its antioxidant and anti-steatotic properties were assessed. Abigenol®/AlbiPhenol® showed an effective antioxidant action, and it was able to inhibit LDL and HDL oxidation, the main actors in atherosclerotic plaque formation. In steatotic conditions, Abigenol®/AlbiPhenol® induces decreased lipid and cholesterol accumulation in hepatocytes. In addition, in a cardiac model, the formulation reduced the activity of the hypertension-related angiotensin-converting enzyme (ACE). Altogether, these findings reveal a potential application of Abigenol®/AlbiPhenol® in the prevention and treatment of CVDs.

Larrea divaricata: anti-inflammatory and antioxidant effects on macrophages and low density lipoproteins

BackgroundThe oxidized low density lipoprotein (ox-LDL) contributes to inflammation and oxidative stress through the activation of macrophages under hyperglycemia contributing to the development of diabetes mellitus and to atherosclerosis. Plants are a source of effective and innocuous antioxidants. Larrea divaricata Cav. (Zygophyllaceae) is used in Argentina folk medicine for its anti-inflammatory properties.MethodsThe aim of this work was to study the antioxidant and anti-inflammatory effects of the aqueous extract (AE) of L. divaricata on macrophages under glucose stimulation and on human LDL and HDL particles under free radical generators. ResultsAE reduced the lipid peroxidation (17%), nitric oxide (NO) (47-50%), tumor necrosis factor-α (TNF-α) (32%) and free radicals (50%) induced by glucose on macrophages. Also prevented HDL nitration (28%), thus preserving its function and structure and inhibited LDL oxidation. The effect on the nitrosative stress was mainly driven by nordihydroguaiaretic acid (NDGA).ConclusionsThese results suggest a potential usefulness of AE as an adjuvant phytotherapy in patients with diabetes mellitus and atherosclerosis.

SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling.

Endothelial cells are an important component of the heart and vasculature and form a crucial link between the cardiovascular system and the immune system. Sestrin 1 (SESN1) has an important role in atherosclerosis by inhibiting NOD-like receptor family pyrin domain containing 3 inflammasome activation. However, whether SESN1 is involved in human umbilical vein endothelial cell (HUVEC) injury caused by atherosclerosis has remained to be elucidated. The present study aimed to investigate the functions of SESN1 in the inflammatory response, apoptosis and endothelial-mesenchymal transition (EndMT) of HUVECs following stimulation with oxidized low-density lipoprotein (Ox-LDL). SESN1 expression at the mRNA and protein levels was detected using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Following SESN1 overexpression in Ox-LDL-stimulated HUVECs, cell viability was determined using a Cell Counting Kit-8 assay. Terminal deoxynucleotidyl transferase-mediated nick-end labeling staining was employed to detect cell apoptosis and western blot analysis was used to determine the levels of apoptosis-related proteins. RT-qPCR, ELISA and western blot were utilized to determine the levels of inflammatory factors. Immunofluorescence staining, RT-qPCR and western blot analysis were employed to assess the EndMT of Ox-LDL-stimulated HUVECs. The results revealed that SESN1 exhibited a low expression in HUVECs following Ox-LDL stimulation. SESN1 overexpression suppressed inflammation, apoptosis and EndMT in Ox-LDL-induced HUVECs. In addition, SESN1 stimulated adenosine monophosphate-activated protein kinase catalytic subunit α1/sirtuin 1 signaling to suppress Ox-LDL receptor-1 expression. An AMPK and SIRT1 inhibitor reversed the effects of SESN1 overexpression on the inflammatory response, apoptosis and EndMT of HUVECs exposed to Ox-LDL. Taken together, the present study demonstrated that SENS1 exerts a suppressive effect on Ox-LDL-induced inflammation, apoptosis and EndMT of HUVECs, suggesting that SENS1 may be used as a novel biomarker for endothelial injury-related disorders.

Effects of Anthocyanin-rich Berries on the Risk of Metabolic Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVEMetabolic syndrome (MetS) can lead to fatal complications, including cardiovascular disease. Emerging evidence suggests has emerged that increased fruit and vegetable intake and decreased intake of saturated fats, simple sugars, and processed foods can improve cardiovascular health. Anthocyanins (color pigments) have anti-inflammatory and antioxidant capacities but are of low bioavailability. In this systematic review and metaanalysis, we investigate the possible beneficial effects of the intake of berries high in anthocyanins on MetS risk factors. We also investigate the influences of high-density lipoprotein (HDL), low- density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC).METHODSWe identified 2,274 articles from PUBMED and EMBASE following a search input designed to include studies of interest of these, 21 met inclusion criteria.RESULTSThe studies showed an overall reduction in low-density lipoprotein (p=0.04). Increases in HDL were found with cranberry and freeze-dried berry intake during a 4-6-week intervention. No statistically significant findings were detected for fasting glucose, Hb1Ac, insulin levels, blood pressure, oxidized LDL (OX-LDL), BMI, and overall HDL.CONCLUSIONSWe conclude from this systematic review and meta-analysis that increased berry intake improves MetS key risk factors and reduces the risk of cardiovascular disease. Pronounced effects were apparent for concentrated berry products, such as freeze-dried strawberries.

S-Nitrosylation of Paraxonase 1 (PON1) Elevates Its Hydrolytic and Antioxidant Activities

Covalent binding between nitric oxide (NO) and a protein’s free thiol group (SH) is termed protein S-nitrosylation. Protein S-nitrosylation is involved in cellular regulation mechanisms that underlie a wide range of critical functions, such as apoptosis, alteration of enzyme activities, and transcription-factor stability. Impaired protein S-nitrosylation is associated with a growing list of pathophysiological conditions, such as cardiovascular disease, multiple sclerosis, pulmonary hypertension, and sickle cell disease. The enzyme paraoxonase 1 (PON1) binds to high-density lipoprotein to provide many of its antiatherogenic properties. The enzyme has a strong antioxidant capacity, which protects fats, lipids, and lipoproteins from oxidation, in addition to breaking down oxidized fats. We investigated the effect of S-S transnitrosylation on PON1 activities. Incubation of recombinant PON1 (rePON1) with nitrosylated human serum albumin (HSA-NO) resulted in S-nitrosylation of about 70% of the rePON1, as measured by Q-TOF LC/MS. S-nitrosylation significantly increased rePON1 hydrolytic activities. It also increased rePON1’s ability to inhibit low-density lipoprotein oxidation induced by Cu2+. Finally, it increased the enzyme’s penetration into macrophage cells by 31%. Our findings suggest that S-nitrosylation of rePON1 improves its biological functions which may positively affect atherosclerosis disease progression.

Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor.

Cardiovascular disease as a result of atherosclerosis is a leading cause of death worldwide. Atherosclerosis is primarily caused by the dysfunction of vascular endothelial cells and the subendothelial accumulation of oxidized forms of low-density lipoprotein (LDL). Early observations have linked oxidized LDL effects in atherogenesis to the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) scavenger receptor. It was shown that LOX-1 is upregulated by many inflammatory mediators and proatherogenic stimuli including cytokines, reactive oxygen species (ROS), hemodynamic blood flow, high blood sugar levels and, most importantly, modified forms of LDL. Oxidized LDL signaling pathways in atherosclerosis were first explored using LDL that is oxidized by copper (Cuox-LDL). In our study, we used a more physiologically relevant model of LDL oxidation and showed, for the first time, that myeloperoxidase oxidized LDL (Mox-LDL) may affect human aortic endothelial cell (HAEC) function through the LOX-1 scavenger receptor. We report that Mox-LDL increases the expression of its own LOX-1 receptor in HAECs, enhancing inflammation and simultaneously decreasing tubulogenesis in the cells. We hypothesize that Mox-LDL drives endothelial dysfunction (ED) through LOX-1 which provides an initial hint to the pathways that are initiated by Mox-LDL during ED and the progression of atherosclerosis.

Antioxidative Effects of Rosuvastatin in Low-to-Moderate Cardiovascular Risk Subjects.

Background: Although vast clinical evidence supports the oxidative CVD hypothesis, little is known on the effects of statins on LDL/HDL oxidative functionality. Therefore, the aim of this study was to evaluate the antioxidative effects of rosuvastatin by monitoring the susceptibility of LDL to oxidation and the antioxidative HDL potential in low-to-moderate CV risk subjects. Methods: 40 adult ambulatory patients (aged 53.8±10.9 years, 27 women and 13 men) were included in the study. Data was collected from patients' records, physical examination, and blood sampling. Subjects were prescribed rosuvastatin at 20mg/day. Traditional risk-factors/indicators, lipid parameters, inflammatory/immune markers, LDL susceptibility to oxidation and HDL antioxidative potential were monitored and statistically analyzed with t-test, Chi-square test, one-way ANOVA, Mann-Whitney, and Kruskal-Wallis tests. Multivariate logistic regression analyses were made. Results were considered significant when p≤0.05. Results: 67% of the patients showed lower susceptibility of LDL to oxidation after rosuvastatin treatment (p=0.03), with no significant effect on baseline LDL oxidation and lag time. All three LDL oxidative indices were seen to be dependent on the subjects' lipid profile, hemoglobin levels and the IL-1α and IL-8 pro-inflammatory marker levels. 53% of the patients showed higher HDL antioxidative capacity after treatment, but without statistical significance (p=0.07). Increased antioxidative potential of HDL with rosuvastatin treatment was more likely in males (OR=9.350; p=0.010), and subjects achieving lower post-treatment CV relative risk levels (higher CV risk reduction) (OR=0.338; p=0.027). Conclusions: This study suggests the need of a comprehensive approach when investigating oxidative stress and LDL/HDL functions, especially in low-to-moderate CVD risk subjects.

MicroRNA miR-34a-5p inhibition restrains oxidative stress injury of macrophages by targeting MDM4.

Atherosclerosis is a chronic cardiovascular disease associated with oxidative stress damage, which is caused by excessive oxidation of low-density lipoprotein (ox-LDL). The role of microRNA miR-34a-5p on oxidative stress in ox-LDL-treated macrophages was investigated in this study. Flow cytometry was prepared for assessing THP1-derived macrophage apoptosis. The protein and expression levels of miR-34a-5p and MDM4 were examined by Western blot and RT-qPCR, respectively. We also measured the levels of total cholesterol (TC) and triglyceride to determine the lipid accumulation. Subsequently, the activities of superoxide dismutase, malondialdehyde, and reactive oxygen species revealed the level of oxidative stress injury after miR-34a-5p and MDM4 knockdown. After ox-LDL treatment, cell apoptosis of macrophages increased in a dose-dependent and time-dependent manner. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of miR-34a-5p was upregulated. Next, interfering with miR-34a-5p inhibited lipid accumulation and oxidative stress injury in ox-LDL-stimulated macrophages. MDM4 was a target gene of miR-34a-5p and was upregulated in ox-LDL-stimulated macrophages. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of MDM4 was downregulated. Importantly, MDM4 knockdown partially counteracted the inhibitory effect of miR-34a-5p on oxidative stress injury. MicroRNA miR-34a-5p knockdown suppressed oxidative stress injury via MDM4 in ox-LDL-treated macrophages.

Iron and Ferritin as novel screening markers of Acute Myocardial Infarction

Introduction: Cardiovascular disease is a public health problem globally. In India, the prevalence of Acute Myocardial Infarction (AMI) was 6.43%. Several causes lead to AMI, among which excess serum Iron and Ferritin is responsible for an increase in the generation of free radicals, thus accelerate atherogenesis through oxidation of Low-density lipoprotein – cholesterol (LDL-C). Assess serum Iron and Ferritin status and compare them with the cardic marker (CK-MB) among patients with AMI. Methods: The study was performed in a tertiary care centre in TamilNadu, India. This casecontrol study was conducted on 25 patients diagnosed with AMI and 25 age and sex-matched healthy participants as control group. Iron, Ferritin, CK-MB and lipid profile parameters were analyzed in serum samples of the participants. Result: The mean levels of serum Iron, Ferritin, CK-MB and lipid profile parameters were increased significantly among the cases when compared to the control group. CK-MB had a strong positive correlation with serum Iron and Ferritin. Serum Iron and Ferritin also had a positive correlation with total cholesterol and LDL-C, and a negative correlation with Highdensity lipoprotein – cholesterol. The odds of developing AMI in those with serum Iron &gt;51.5µg/dl and Ferritin &gt;137ng/dl were 36 and 61.7 times at higher risk respectively. Conclusion: Higher levels of serum Iron and Ferritin seem to be stronger risk factors for AMI, and shall be considered as early screening cardiac markers for AMI.

Biomarkers of endothelial activation and dysfunction in cardiovascular diseases.

Endothelial activation and dysfunction is an important contributor to atherosclerosis, cardiovascular diseases and cardiorenal syndrome. Endothelial dysfunction is also linked with metabolic syndrome and type II diabetes. The search for specific and sensitive biomarkers of endothelial activation and dysfunction may have important clinical implications. This review pinpoints the differences in biomarkers between endothelial activation and endothelial dysfunction in cardiovascular diseases, and then briefly describes the most relevant biomarkers of endothelial activation. Biomarkers of endothelial activation include endothelial adhesion molecules, cytokines, C-reactive protein, CD62E+/E-selectin activated endothelial microparticles, oxidation of low density lipoproteins, asymmetric dimethylarginine and endocan. This review also presents an update on the novel biomarkers of endothelial dysfunction, such as matrix metalloproteinases (e.g., MMP-7, MMP-9), ANGPTL2, endogdlin, annexin V+ endothelial apoptotic microparticles, and serum homocysteine. Finally, this review emphasizes the limitations of biomarkers of endothelial activation and dysfunction in clinical setting.

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Can paraoxonase activity serve as a comparable marker than high density lipoprotein in the follow-up of patients of coronary artery disease?

Abstract Funding Acknowledgements Type of funding sources: None. Background Human serum paraoxonase (PON1) produced by the liver and residing almost exclusively on high density lipoproteins (HDL), has been demonstrated to prevent the oxidation of low density lipoprotein (LDL), which is the central initiating factor in the causation of atherosclerosis. (1,2) Thus, PON1 along with HDL, plays an important role in the pathophysiology of atherosclerosis and consequently coronary artery disease. Statins are commonly used in clinical practice for the management of dyslipidemia , a known risk factor for coronary artery disease (CAD).Keeping this in mind, it was deemed necessary to set up an observational study to explore whether the changes in PON1 activity after 3 months of statin therapy could help in the follow up of CAD patients. Purpose The purpose of the study was to evaluate the alterations in the PON1 activity along with the concentrations of HDL and LDL in patients of CAD before and after 3 months of statin therapy and to explore whether PON1 can be used as a comparable marker for assessment of the atherosclerotic risk in the follow up of these patients. Materials and Methods The study included 30 new patients who were put on statin therapy following the diagnosis of acute coronary syndrome in the Cardiology outpatients department. The activity of PON1 and the lipid profile parameters were estimated before starting statin therapy and again three months later. Patients with co-morbidities like diabetes, chronic kidney disease, chronic liver disease and other cardiac diseases of infectious etiology were excluded from the study. The data thus obtained was compiled and tabulated in Excel and statistically analyzed. Results The mean, median and standard deviation of the PON1, LDL and HDL, both before and after starting statin therapy, were calculated and the distribution of the individual parameters were determined. Analysis of the compiled data revealed that there was a statistically significant increase in both PON1 (p &amp;lt; 0.05) and HDL (p &amp;lt; 0.001) and a decrease (p &amp;lt;0.05, also statistically significant) in LDL after 3 months of statin therapy. The results both before and after 3 months of statin therapy are summarised in the table attached.(Table 1) Conclusion It may be concluded from the above study that the activity of PON1 may be used to indicate the changes in the lipid profile in the follow up of patients of CAD being treated with statins. It is however necessary to conduct larger, well designed studies in future to explore whether it may be used as a comparable marker better than HDL in the follow up of these patients. Abstract Figure.

Regulatory Mechanism of MicroRNA-9 / Long Non-Coding RNA XIST Expression on Mouse Macrophage RAW264.7 Apoptosis Induced by Oxidized Low Density Lipoprotein

ABSTRACT It aims to analyze the influential mechanism of microRNA-9 (miR-9) and long non-coding RNA XIST (lncRNA XIST) expression on the proliferation and apoptosis of macrophages induced by oxidized-low density lipoprotein (ox-LDL). Firstly, lncRNA XIST overexpression vector was constructed, and then RAW264.7 cells were used as the research object. Methylthiazolyl tetrazolium (MTT) method, flow cytometry, and Western blot were used to detect and compare the differences of cell proliferation, apoptosis, and the expression levels of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), matrix metalloproteinase-9 (MMP-9), and B-cell lymphoma-2 (Bcl-2) after ox-LDL induction and transfection of miR-9 mimic, miR-9 inhibitor and XIST expression vector, respectively. The results showed that lncRNA XIST overexpression vector was successfully constructed and transfected into cells, wh5ich can inhibit the expression level of miR-9. Compared with the normal control group, ox-LDL can inhibit cell proliferation, promote cell apoptosis, and increase the expression level of target protein. Moreover, transfection of XIST expression vector based on ox-LDL induction can significantly enhance the inhibition of cell proliferation, and promote cell apoptosis and the expression of target protein. Transfection of miR-9 mimic can improve the biological changes induced by ox-LDL. After co-transfection of miR-9 mimic and XIST expression vector based on ox-LDL induction, cell proliferation, apoptosis, and target protein expression level were not significantly different from those induced by ox-LDL alone. In summary, the increased expression level of miR-9 can inhibit the apoptosis of macrophages induced by ox-LDL. lncRNA XIST can positively regulate the apoptosis of macrophages induced by ox-LDL.